Structure-activity relationship of berberine and derivatives acting as antifungal compounds

A structure-activity relationship study of berberine and structurally related compounds is reported. Berberine, was chemically modified in order to obtain canadine and oxyberberine. The in vitro evaluation of antifungal activity of berberine, canadine, oxyberberine, liriodenine, o-methyl-mostachatoline and other four derivatives is also reported here. Our results allow us to determine the minimal structural requirements to produce the antifungal response and can provide a guide for the design of new compounds with these properties.Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Freile, Monica Liliana. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentin

Structural and thermodynamic characteristics of the exosite binding pocket on the human BACE1: A molecular modeling approach

We report a molecular modeling study aimed to locate and provide the full structural characteristics of the exosite binding site of the BACE1. A three-step procedure was followed. In the first stage, we performed blind docking studies on the whole target surface. In a second stage, the mode of binding was further refined by molecular dynamics (MD) simulation. Finally, binding free energy calculations, through the MM-PBSA protocol, were carried out to gain insight into the stability and thermodynamics of the inhibitor located at the selected binding pockets. Twelve binding pockets were identified on the surface of BACE1 by blind docking studies. The calculations of binding free energies for the 12 complexes show that van der Waals interactions dominate the mode of binding of these complexes. The best ranked complex shows that residues Glu255-Pro258, Phe261, Gly264-Ala272, Asp311-Ala313, Ser315, and Asp317-Tyr320 are located within ∼6 Å from the INH located at the exosite. The hydrogen bonds formed between the INH peptide, residues Tyr1, Tyr3, and Leu7 with the BACE1 residues Leu267, Cys269, Trp270, Asp311, and Asp 317 can strengthen the binding of the BACE1-INH complex.Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; ArgentinaFil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; Argentin

Ab Initio and DFT Study of the conformational Energy Hypersurface of cyclic Gly-Gly-Gly

The multidimensional conformational potential energy hypersurface (PEHS) of cyclic Gly-Gly-Gly (1,4,7triazonane-2,5,8-trione) was comprehensively investigated at the Hartree-Fock (RHF/6-31G(d)) level of theory. The equilibrium structures, their relative stability, and the transition state (TS) structures involved in the conformational interconversion pathways were analyzed. aug-cc-pVTZ//B3LYP/6-311++G** single point calculations predict a trans-cis-cis conformation as the energetically preferred form for this compound. However, all of the levels of theory employed here predicted that two forms, a trans-cis-cis and a cis-cis-cis (crown), of conformers contribute significantly to the equilibrium mixture at room temperature. The conformational interconversion between the global minimum and the symmetric cis-cis-cis crown form requires 12.49 kcal/mol at the RHF 6-31G(d) level of theory, whereas the conformational interconversion between the cis-cis-cis crown and cis-cis-cis boat form requires 18.70 kcal/mol. An exploratory topological analysis of the PEHS was also carried out. Our results allow us to form a concise idea about the internal intricacies of the PEHSs of these cyclic tripeptides, describing the conformations as well as the conformational interconversion processes in these hypersurfaces.Fil: Tosso, Rodrigo David. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Zamora, Miguel Angel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Suvire, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; ArgentinaFil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Área Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Covalence and π-electron delocalization influence on hydrogen bonds in proton transfer process of o-hydroxy aryl Schiff bases: A combined NMR and QTAIM analysis

Within the framework of the density functional theory approach, we studied the relationship between the chemical nature of intramolecular hydrogen bonds (HBs) and nuclear magnetic resonance (NMR) parameters, J-couplings and 1H-chemical shifts [δ(1H)], of the atoms involved in such bonds in o-hydroxyaryl Schiff bases during the proton transfer process. For the first time, the shape of the dependence of the degree of covalence in HBs on 1J(N-H), 1J(O-H), 2hJ(O-N), and δ(1H) during the proton transfer process in o-hydroxyaryl Schiff bases was analyzed. Parameters obtained from Bader's theory of atoms in molecules were used to assess the dependence of covalent character in HBs with both the NMR properties. The influence of π-electronic delocalization on 2hJ(N-O) under the proton transfer process was investigated. 2hJ(O-N) in a Mannich base was also studied in order to compare the results with an unsaturated system. In addition, substituent effects on the phenolic ring were investigated. Our results indicate that the covalent character of HBs on both sides of the transition state undergoes a smooth exponential increase as the δ(1H) moves downfield. The degree of covalence of the N⋯H (O⋯H) bond increases linearly as 1J(N-H) (1J(O-H)) becomes more negative, even after reaching the transition state. Non-vanishing values of spin dipolar (SD) and paramagnetic spin orbital terms of 2hJ(O-N) show that π-electronic delocalization has a non-negligible effect on tautomeric equilibrium and gives evidence of the presence of the resonance assisted HB.Variation of the SD term of 2hJ(O-N) follows a similar pattern as the change in the para-delocalization aromaticity index of the chelate ring.Fil: Zarycz, Maria Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Schiel, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Structure of isolated tyrosyl-glycyl-glycine tripeptide. A comparative conformational study with peptides containing an aromatic ring

The potential energy surface (PES) of tyrosyl-glycyl-glycine (YGG) tripeptide in solution was explored using EDMC (Electrostatically Driven Monte Carlo) and in the gas-phase by means of ab initio quantum chemical calculations. The theoretical computational analysis revealed that this tripeptide possesses a significant molecular flexibility. A C7 backbone conformation was the most energetically preferred for the central Gly residue, using both methodologies. Some new stable conformers that have not been previously reported were identified in the gas phase as well. This study points out the interplay of backbone and side-chain contributions in determining the relative stabilities of energy minima. In addition, the peptide backbone of YGG was compared with other small peptides containing aromatic side-chains (Phe-Gly-Gly and Trp-Gly-Gly). The comparison with experimental X-ray results was also satisfactory.Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Masman, Marcelo Fabricio. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Rodríguez, Ana M.. Universidad Nacional de San Luis; Argentin

An exploratory conformational analysis of 3-mercapto-propanamide and 2-methyl-3-mercapto-propanamide as well as their S-deprotonated conjugate basis: An ab initio study

Ab initio conformational analysis has been carried out on 3-mercapto-propanamide, (R)- and (S)-2-methyl-3-mercaptopropanamide as well as their S-deprotonated conjugate basis. They were carried out at the HF/3-21G level of theory. The topology of the conformational potential energy surfaces and hypersurfaces have been analysed.Fil: Torday, László L.. Albert Szent-Györgyi Medical University; HungríaFil: Penke, Botond. Albert Szent-Györgyi Medical University; HungríaFil: Zamarbide, Graciela Nidia. Universidad Nacional de San Luis; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Papp, Julius Gy. Albert Szent-Györgyi Medical University; Hungrí

Theoretical study of the conformational energy hypersurface of cyclotrisarcosyl

The multidimensional Conformational Potential Energy Hypersurface (PEHS) of cyclotrisarcosyl was comprehensively investigated at the DFT (B3LYP/6-31G(d), B3LYP/6-31G(d,p) and B3LYP/6-311++G(d,p)), levels of theory. The equilibrium structures, their relative stability, and the Transition State (TS) structures involved in the conformational interconversion pathways were analyzed. Aug-cc-pVTZ//B3LYP/6-311++G(d,p) and MP2/6-31G(d)//B3LYP/6-311++G(d,p) single point calculations predict a symmetric cis-cis-cis crown conformation as the energetically preferred form for this compound, which is in agreement with the experimental data. The conformational interconversion between the global minimum and the twist form requires 20.88 kcal mol-1 at the MP2/6-31G(d)//B3LYP/6- 311++G(d,p) level of theory. Our results allow us to form a concise idea about the internal intricacies of the PEHSs of this cyclic tripeptide, describing the conformations as well as the conformational interconversion processes in this hypersurface. In addition, a comparative analysis between the conformational behaviors of cyclotrisarcosyl with that previously reported for cyclotriglycine was carried out.Fil: Alvarez, Maria de Los Angeles. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Saavedra, Edgardo J.. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Olivella, Mónica Susana. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Zamora, Miguel Angel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentin

Easy synthesis of new series of pteridine analogs: di- and tetra-hydropyrimido[4,5-d]pyrimidines via 5-pyrimidinecarbaldehydes

Pyrimidine-5-carbaldehyde derivatives, of easy access, were selected as precursors for the synthesis of mimic pteridine derivatives 5,6-dihydropyrimido[4,5-d]pyrimidines and 5,6,7,8- tetrahydropyrimido[4,5-d]pyrimidines via 4-amino-(5-aminomethyl)pyrimidine intermediates. Straightforward procedures allow a quick access to these compounds. The dihydro derivatives were prepared means of a final cyclocondensation carried out with orthoesters, catalysed by acid and assisted by microwaves irradiation under solvent free conditions. The final cyclocondensation with carbonyl compounds forming the tetrahydro derivatives was done under mild conditions, in which stereochemical induction was carried out on the building of this skeleton, and stereochemistry assignments corroborated by theoretical calculations.Fil: de la Torre, José M.. Universidad de Jaén; EspañaFil: Nogueras, Manuel. Universidad de Jaén; EspañaFil: Borkowski, Eduardo Jorge. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Suvire, Fernando D.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cobo, Justo. Universidad de Jaén; Españ

Fish toxicity of commercial herbicides formulated with glyphosate

We report here the acute and chronic toxicity of two commercial formulations of herbicides whose active ingredient is glyphosate (Glacoxan® and Estrella®). The acute toxicity was tested toward two fish species Danio rerio and Poecilia reticulata by evaluating the mortality. The chronic toxicity was assessed in D. rerio by measuring the biochemical parameters glutamic pyruvic transaminase (AST) and glutamic oxaloacetic transaminase (ASL). In addition the analysis of haematological parameters (morphological study) was carried out. The results indicate that both herbicides produce acute toxicity toward the two tested species. In addition the biochemical parameters displayed high values as a sign of chronic toxicity. Thereby, indicating that both herbicides may produce environmental damage.Fil: Jofré, Diego Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Germanó García, María José. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Salcedo, Rodrigo Emiliano. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morales, Mirta. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Alvarez, María. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gianinni, Fernando. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentin

Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation

Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1-16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1-3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.Fil: Hudcová, Anna. University Of Veterinary And Pharmaceutical Sciences; República ChecaFil: Kroutil, Ales. University Of Veterinary And Pharmaceutical Sciences; República ChecaFil: Kubínová, Renata. University Of Veterinary And Pharmaceutical Sciences; República ChecaFil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Oravec, Michal. Global Change Research Institute; República ChecaFil: Csöllei, Jozef. University Of Veterinary And Pharmaceutical Sciences; República Chec